Targeting cyclooxygenase-2 in human neoplasia: Rationale and promise
Targeting cyclooxygenase-2 in human neoplasia: Rationale and promise
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DOI：
10.1016/s1535-6108(03)00310-6
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发表时间：
2003-12-01
期刊：
影响因子：
50.3
通讯作者：
Subbaramaiah, K
中科院分区：
文献类型：
--
作者：
Dannenberg, AJ;Subbaramaiah, K
多项证据表明环氧合酶-2 (COX-2) 是抗癌治疗的合理靶点。流行病学研究表明，使用非甾体抗炎药 (NSAID)（COX 原型抑制剂）可降低多种恶性肿瘤的风险（Thun 等，2002）。在最近的一项观察性研究中，发现 COX-2 的选择性抑制剂可以预防结直肠肿瘤的发展（Rahme 等，2003）。与这些发现一致的是，在用选择性 COX-2 抑制剂治疗或改造为 COX-2 缺陷的动物中，肿瘤形成和生长减少。选择性 COX-2 抑制剂已广泛用于治疗关节炎患者，并具有出色的安全性。基于这些发现，大量临床试验正在进行中，以研究选择性 COX-2 抑制剂在预防和治疗多种癌症中的潜在功效。在这里，我们重点讨论以 COX-2 作为预防或治疗人类恶性肿瘤的策略的基本原理。
Several lines of evidence suggest that cyclooxygenase-2 (COX-2) is a rational target for anticancer therapy. Epidemiological studies have shown that use of nonsteroidal anti-inflammatory drugs (NSAIDs), prototypic inhibitors of COX, is associated with a reduced risk of several malignancies (Thun et al., 2002). In a recent observational study, selective inhibitors of COX-2 were found to protect against the development of colorectal neoplasia (Rahme et al., 2003). Consistent with these findings, tumor formation and growth were reduced in animals treated with selective inhibitors of COX-2 or engineered to be COX-2-deficient. Selective COX-2 inhibitors have been used extensively to treat patients with arthritis and possess an excellent safety profile. Based on this constellation of findings, numerous clinical trials are under way to investigate the potential efficacy of selective COX-2 inhibitors in the prevention and treatment of a variety of cancers. Here we focus on the rationale for targeting COX-2 as a strategy to prevent or treat human malignancies.